Wellcome to the PBPath Journal Watch!
This bi-monthly journal watch features exciting recently published pancreas and biliary pathology articles that will provide up to date medical knowledge in our field. These articles will be showcased in several convenient categories, including surgical pathology, molecular pathology and cytopathology among others. The articles in each category are in no particular order.
Previous months’ issues may be found in our archive.
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We hope that you will enjoy the new PBPath Journal Watch!
Morphology, Diagnostics, IHC
- Malformations, choristomas, and hamartomas of the gastrointestinal tract and pancreas
Seminars in diagnostic pathology 2018 Nov;():
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30482417
Congenital and hamartomatous lesions of the gastrointestinal tract cause diagnostic challenges for surgical pathologists. Many of these are merely histologic curiosities, whereas others have substantial clinical implications because they herald cancer syndromes or associated anomalies. Although a comprehensive discussion of all developmental abnormalities that can occur in the gastrointestinal tract is beyond the scope of a single manuscript, some entities are more likely to be encountered by surgical pathologists, have important clinical consequences, or pose diagnostic difficulties. The purpose of this review is to discuss the more common malformations and choristomas, as well as hamartomatous lesions that may be clinically important due to their risk for cancer development, frequent associations with heritable cancer syndromes and other anomalies, or potential to simulate other entities.
https://www.sciencedirect.com/science/article/pii/S0960740418301245
Pancreas TNM staging, Margins, Survival
https://onlinelibrary.wiley.com/doi/abs/10.1002/jso.25312
Preneoplastic and Preinvasive Lesions, PanIN, IPMN, MCN, ICPN
- New Model for Predicting Malignancy in Patients With Intraductal Papillary Mucinous Neoplasm
Annals of surgery 2018 Nov;():
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30499803
OBJECTIVE: To create a simple, objective model to predict the presence of malignancy in patients with intraductal papillary mucinous neoplasm (IPMN), which can be easily applied in daily practice and, importantly, adopted for any lesion types. BACKGROUND: No predictive model for malignant IPMN has been widely applied in clinical practice. METHODS: The clinical details of 466 patients with IPMN who underwent pancreatic resection at 3 hospitals were retrospectively analyzed for model development. Then, the model was validated in 664 surgically resected patients at 8 hospitals in Japan.In the preoperative examination, endoscopic ultrasonography (EUS) was considered to be essential to observe mural nodules in both the model development and external validation sets. Malignant IPMNs were defined as those with high-grade dysplasia and associated invasive carcinoma. RESULTS: Of the 466 patients, 258 (55%) had malignant IPMNs (158 high-grade dysplasia, 100 invasive carcinoma), and 208 (45%) had benign IPMNs. Logistic regression analysis resulted in 3 variables (mural nodule size, main pancreatic duct diameter, and cyst size) being selected to construct the model. The area under the receiver operating characteristic curve (AUC) for the model was 0.763. In external validation sets, the pathological diagnosis was malignant and benign IPMN in 351 (53%) and 313 (47%) cases, respectively. For the external validation, the malignancy prediction ability of the model corresponded to an AUC of 0.725. CONCLUSION: This predictive model provides important information for physicians and patients in assessing an individual’s risk for malignancy and may help to identify patients who need surgery.
https://journals.lww.com/eurojgh/Abstract/2019/01000/The_efficacy_and_safety_of_endoscopic.1.aspx
https://www.sciencedirect.com/science/article/pii/S0021997518302020
- Clinicopathological and immunological features of follicular pancreatitis-a distinct disease entity characterized by Th17 activation
Histopathology 2018 Dec;():
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30515871
AIM: Follicular pancreatitis is a recently recognized, distinct clinicopathological entity characterized by the presence of many intrapancreatic lymphoid follicles with reactive germinal centres. However, the clinicopathological and immunological features and causes have not yet been established. We assessed the clinicopathological and immunological profiles of patients with follicular pancreatitis who underwent surgery. METHODS AND RESULTS: This study included three patients with pancreatic masses (age range: 62-75 years; women:men: 1:2). A histopathological study of the resected pancreatic masses revealed abundant lymphoid follicles with reactive germinal centres in both periductal regions and diffusely within the parenchyma. No storiform fibrosis, obliterative phlebitis, or granulocytic epithelial lesions were observed. The immunohistochemical examination revealed an IgG4/IgG-positive plasma cell ratio <30% in all patients. Podoplanin (Th17 marker)-expressing lymphocytes were present in the lymphoid follicles of those with follicular pancreatitis, whereas these were absent in normal lymph nodes and in lymphoid follicles of those with IgG4-related autoimmune pancreatitis (AIP). An RNA digital counting assay clearly demonstrated that the expression counts of 20 genes, including dendritic cells and lymphoid follicles markers, and related cytokines were significantly higher in follicular pancreatitis than in IgG4-related AIP (p<0.01). The expressions of CCR6 and IL23A, which are genes related to Th17, were high. CONCLUSIONS: This study shows that follicular pancreatitis is a histopathologically and immunologically distinct disease entity of pancreatitis and is characterized by upregulated Th17 expression. This article is protected by copyright. All rights reserved.
https://www.hindawi.com/journals/bmri/2018/7169595/
- Circulating interleukin-6 is associated with disease progression, but not cachexia in pancreatic cancer
Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2018 Nov;():
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30497874
BACKGROUND: Cachexia is a wasting syndrome characterized by involuntary loss of >5% body weight due to depletion of adipose and skeletal muscle mass. In cancer, the pro-inflammatory cytokine interleukin-6 (IL-6) is considered a mediator of cachexia and a potential biomarker, but the relationship between IL-6, weight loss, and cancer stage is unknown. In this study we sought to evaluate IL-6 as a biomarker of cancer cachexia while accounting for disease progression. METHODS: We retrospectively studied 136 subjects with biopsy-proven pancreatic ductal adenocarcinoma (PDAC), considering the high prevalence of cachexia is this population. Clinical data were abstracted from subjects in all cancer stages, and plasma IL-6 levels were measured using a multiplex array and a more sensitive ELISA. Data were evaluated with univariate comparisons, including Kaplan-Meier survival curves, and multivariate Cox survival models. RESULTS: On multiplex, a total of 43 (31.4%) subjects had detectable levels of plasma IL-6, while by ELISA all subjects had detectable IL-6 levels. We found that increased plasma IL-6 levels, defined as detectable for multiplex and greater than median for ELISA, were not associated with weight loss at diagnosis, but rather with the presence of metastasis (p < 0.001 for multiplex and p = 0.007 for ELISA). Further, while >5% weight loss was not associated with worse survival, increased plasma IL-6 by either methodology was. CONCLUSION: Circulating IL-6 levels do not correlate with cachexia (when defined by weight loss), but rather with advanced cancer stage. This suggests that IL-6 may mediate wasting, but should not be considered a diagnostic biomarker for PDAC-induced cachexia.
https://hccpjournal.biomedcentral.com/articles/10.1186/s13053-018-0100-6
- Dietary Fiber and the Risk of Pancreatic Cancer
Pancreas 2018 Nov;():
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30489447
OBJECTIVES: High dietary fiber may protect against pancreatic ductal adenocarcinoma (PDA). We investigated associations between fiber intake and the risk of PDA using for the first time 7-day food diaries. METHODS: Participants in the European Prospective Investigation Into Cancer-Norfolk completed the 7-day food diaries at recruitment. The cohort was followed up for 17 years to identify those who developed PDA. Participants were divided into quintiles of fiber intake, and hazard ratios (HR) were estimated with their 95% confidence intervals (CIs). Fiber was tested for effect modification of high red and processed meat intakes and smoking and the risk of PDA. RESULTS: No significant associations for any quintiles of intake (HR Q5 vs Q1,1.08; 95% CI, 0.56-2.08) were detected with no trend across quintiles. A high-fiber diet modified positive associations between red and processed meats with the development of PDA (HR trends, 0.89 [95% CI, 0.47-1.69] and 1.02 [95% CI, 0.55-1.88], respectively) but not those with lower fiber intakes. Fiber intake did not modify the risk of PDA in past and current smokers. CONCLUSION: The findings do not suggest that fiber protects against PDA, although it may decrease potential deleterious effects of meats.
- Nomogram to Predict Cancer-Specific Survival in Patients with Pancreatic Acinar Cell Carcinoma: A Competing Risk Analysis
Journal of Cancer 2018 10;9(22):4117-4127
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30519311
Background: The objective of this study was to evaluate the probability of cancer-specific death of patients with acinar cell carcinoma (ACC) and build nomograms to predict overall survival (OS) and cancer-specific survival (CSS) of these patients. Methods: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Patients diagnosed with ACC between 2004 and 2014 were retrospectively collected. Cancer-specific mortality and competing risk mortality were evaluated. Nomograms for estimating 1-, 2- and 3-year OS and CSS were established based on Cox regression model and Fine and Grey’s model. The precision of the 1-, 2- and 3-year survival of the nomograms was evaluated and compared using the area under receiver operating characteristic (ROC) curve (AUC). Results: The study cohort included 227 patients with ACC. The established nomograms were well calibrated, and had good discriminative ability, with a concordance index (C-index) of 0.742 for OS prediction and 0.766 for CSS prediction. The nomograms displayed better discrimination power than 7th or 8th edition Tumor-Node-Metastasis (TNM) stage systems in training set and validation set for predicting both OS and CSS. The AUC values of the nomogram predicting 1-, 2-, and 3-year OS rates were 0.784, 0.797 and 0.805, respectively, which were higher than those of 7th or 8th edition TNM stage systems. Regard to the prediction of CSS rates, the AUC values of the nomogram were also higher than those of 7th or 8th edition TNM stage systems. Conclusion: We evaluated the 1-, 2- and 3-year OS and CSS in patients with ACC for the first time. Our nomograms showed relatively good performance and could be considered as convenient individualized predictive tools for prognosis.
- Systematic review and meta-analysis: Prevalence of incidentally detected pancreatic cystic lesions in asymptomatic individuals
Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2018 Nov;():
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30503370
BACKGROUND & AIMS: Pancreatic cystic lesions (PCLs) are frequent incidental findings. As most PCLs require costly diagnostic evaluation and active surveillance, it is important to clarify their prevalence in asymptomatic individuals. We therefore aimed at performing a systematic review and meta-analysis to determine it. METHODS: a systematic search was conducted and studies meeting inclusion criteria were included. The prevalence of PCLs was pooled across studies. A random effect model was used with assessment of heterogeneity. RESULTS: 17 studies, with 48,860 patients, were included. Only 3 were prospective; 5 studies were conducted in the US, 7 in Europe, 4 in Asia and 1 in Brazil. The pooled prevalence of PCLs was 8% (95% CI 4-14) with considerable heterogeneity (I2 = 99.5%). This prevalence was higher in studies of higher quality, examining older subjects, smaller cohorts, and employing MRCP (24.8% vs 2.7% with CT-scan). The pooled rate of PCLs was four times higher in studies conducted in the US than in Asia (12.6% vs 3.1%). 7 studies reported the prevalence of mucinous lesions, with a pooled rate of 4.3% (95% CI 2-10; I2 = 99.2%), but of 0.7% only for worrisome features or high risk stigmata. CONCLUSION: The rate of incidentally detected PCLs is of 8%. Mucinous lesions are the most common incidentally detected PCLs, although they rarely present with potential indication for surgery. The observed different rates in the US and other geographic Areas suggest that different protocols might be necessary to help balancing costs and effectiveness of follow-up investigations in asymptomatic subjects.
- Tumor growth rate of pancreatic serous cystadenomas: Endosonographic follow-up with volume measurement to predict cyst enlargement
Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2018 Nov;():
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30503637
BACKGROUND: Serous cystadenomas are benign lesions of the pancreas. Usually they are diagnosed incidentally on cross-sectional imaging studies. Endosonography is a valuable tool in the diagnosis and follow-up of these cystic lesions. Given its benign nature, surgical resection is advised only in symptomatic patients. The interval and length of surveillance is not well established. METHODS: A retrospective single center study was done. All the patients with a pancreatic serous cystadenoma sent for an endosonographic evaluation, between December 2008 and December 2015 were included. The lesions were follow-up endosonographically at least once, in a 12 months interval. Volume was measured with the formula π/6 × (d1 x d1 x d2). Two groups were evaluated: patients with a volume under 10 mL (Group 1) and those with a volume of 10 mL or more at presentation (Group 2). Growth rate between these two groups was compared. RESULTS: Thirty-one patients were analyzed, with a mean age of 58.2 years. Patients were mainly women (87%). Twenty-four patients in Group 1 had a mean enlargement of 0.67 ml per year, whereas patients in Group 2 had a mean enlargement of 9.8 ml per year. The growth rate difference between these two groups was statistically significant (p = 0.0001). CONCLUSION: Asymptomatic patients with pancreatic serous cystadenomas should be follow-up for enlargement. Small volume lesions have a low risk of enlargement compared with high volume and macrocystic serous cystadenomas. Volume at presentation is a feature to analyze when defining surveillance interval.
https://link.springer.com/article/10.1007/s12328-018-00928-w
- Cholangiolocellular Carcinoma With “Ductal Plate Malformation” Pattern may be Characterized by ARID1A Genetic Alterations
The American journal of surgical pathology 2018 Dec;():
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30520820
Cholangiolocellular carcinoma (CLC) is a unique subtype of primary liver carcinoma, which sometimes coexists with hepatocellular carcinoma (HCC), cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma (cHCC-CCA). “Ductal plate malformation” (DPM)-pattern of primary liver carcinoma, which resembles biliary lesions in Caroli disease and von Meyenburg complex, is sometimes associated with CLC. We examined genetic alterations of hTERT promoter (hTERT), IDH1 or 2 (IDH1/2), KRAS, ARID1A, PBRM1, ARID2, BAP1, p53 and their association with histologic features such as proportion of CLC and DPM-pattern in 77 patients with primary liver carcinoma diagnosed as cHCC-CCA or CLC. Primary liver carcinomas were histologically subdivided into 29 CLC-predominant (CLC component >80%), 31 with CLC (5% to 80%) and 17 without CLC (<5%). CLC-predominant group was characterized by older age, male-predominant and smaller tumor size. Genetic alterations were detected in hTERT (25%), ARID1A (21%), PBRM1 (20%), ARID2 (3%), BAP1 (1%), p53 (46%), KRAS (5%), and IDH1/2 (8%). ARID1A alteration was more frequent in CLC-predominant group, compared with other groups (P<0.05) and was correlated with the degree of DPM-pattern (P<0.01). Alterations of hTERT and p53 were less frequent in CLC-predominant group compared with “with CLC group” (P<0.05). hTERT mutation was less frequent in carcinomas with DPM-pattern (P<0.01). PBRM1 alteration was more frequent in CLC with focal HCC subgroup and without CLC group compared with other groups (P<0.05). CLC may be a distinct subgroup of primary liver carcinoma, which is different from cHCC-CCA, based on clinicopathologic and genetic alterations. ARID1A alterations may characterize CLC with DPM-pattern and could be a diagnostic immunohistochemical marker for small CLCs with DPM-pattern.
https://www.sciencedirect.com/science/article/pii/S0022480418307753
- EBV as a potential risk factor for hepatobiliary system cancer: A meta-analysis with 918 cases
Pathology, research and practice 2018 Nov;():
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30497878
OBJECTIVES: Hepatobiliary system cancer, which includes hepatocellular carcinoma (HCC), cholangiocarcinoma, and gallbladder carcinoma, has an increase of incidence and mortality due to various risk factors. Epstein-Barr virus (EBV) is associated with various types of lymphomas and carcinomas, which is also acknowledged as the first-discovered human tumor virus. Despite this, there is no systematic analysis about the relationship between the infection of EBV and hepatobiliary system cancer. The aim of this meta-analysis is to explore the significance of EBV infection in the development of hepatobiliary system cancer by evaluating the EBV infection ratio. METHODS: A systematic search of PubMed, Embase, Cochrane Library, as well as China National Knowledge Infrastructure (CNKI), Chongqing VIP, Wan Fang, and China Biology Medicine databases was conducted. The EBV infection ratio and 95% confidence intervals (CIs) in hepatobiliary system cancer was evaluated. The I2 statistic was used to represent heterogeneity. Through meta-regression, stratified analyses were applied to find out heterogeneity’s sources. Odds ratios (ORs), 95% CIs of EBV infection in case-control studies were calculated. RESULTS: Altogether, 15 studies were included containing a total of 918 cases and 157 controls. The whole infection ratio of EBV was 23% (95% CI: 13%, 33%, I2 = 95.7%, P < 0.001) among all the patients. Comparable EVB infection ratios were observed in hepatobiliary system cancer as divided into different subtypes. The five case-control studies were epitomized to a pooled OR of 9.35 (95%CI: 2.95, 29.61, I2 = 20.1%, P < 0.286). CONCLUSION: EBV may be a potentially risk factor in the process of hepatobiliary system cancer. The prospective molecular mechanism remains to be explored.
- Current survival and treatment trends for surgically resected intrahepatic cholangiocarcinoma in the United States
Journal of gastrointestinal oncology 2018 Oct;9(5):942-952
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30505597
Background: Intrahepatic cholangiocarcinoma (ICC) is a rare and aggressive disease with an increasing incidence in the United States, and there is no level 1 evidence to help guide treatment decisions. We sought to determine national trends in surgical and medical management of patients with resected ICC, and more specifically, the role of lymphadenectomy (LAD) and utilization of chemotherapy. Methods: An augmented version of the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) cancer database registry was used to identify all surgically resected ICC patients from 2000 to 2014. We evaluated the incidence and adequacy of LAD, and receipt of chemotherapy over time. Next, multivariable logistic regressions were performed to determine the predictors of LAD and receipt of chemotherapy. Overall survival (OS) was evaluated using Kaplan-Meier and Cox proportional hazard models. Results: We identified 1,263 patients who underwent resection for ICC. Lymph nodes (LNs) were removed in 49% of patients, however, only 10% of patients received adequate LAD by the American Joint Committee on Cancer (AJCC) criteria (≥6 nodes). LN metastases were found in 29% of patients who underwent nodal evaluation. Chemotherapy was administered to 40% of patients, was utilized more frequently over time (P<0.05), and was associated with improved survival in node positive patients (P<0.05). Patients who did not have LNs evaluated were significantly less likely to receive chemotherapy than those who did. Lastly, OS for the entire cohort improved over time (P<0.05). Conclusions: After analyzing the treatment and outcomes of resectable ICC, we concluded: (I) LN evaluation at the time of surgical resection remains inadequate; (II) utilization of chemotherapy has increased over time; (III) the lack of LAD likely results in under-staging and underutilization of chemotherapy; and (IV) despite less than ideal surgical and medical therapy median OS continues to improve.
Morphology, Diagnostics, IHC
- Importance of routine histopathological examination of a gallbladder surgical specimen: Unexpected gallbladder cancer
Journal of cancer research and therapeutics 2018 11;14(6):1325-1329
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30488851
Introduction: Cholecystectomy performed for benign diseases of the gallbladder is important for the diagnosis of gallbladder cancer. This is done by pathological examination of the removed specimens for patients with no detected or suspected complications before surgery. Although some centers undertake selective approaches for histopathological examination of gallbladder specimens, many centers perform this examination routinely. In our study, we investigated results of pathological examinations carried out on cholecystectomy specimens, in respect to unexpected cases of gallbladder cancer. Methods: We reviewed cholecystectomy cases performed for benign diseases of gallbladder from January 2012 to February 2016 by investigating pathological specimens from the gallbladder. We evaluated demographical properties and their association with the pathological diagnosis and frequency of unexpected gallbladder cancer cases. We reported additional treatment and survival information of the malignancy cases after surgery. Results: We reviewed 1294 cases of cholecystectomy, and the mean patient age was 47.5 ± 14.3 years. The most frequent diagnosis was chronic cholecystitis (92.3%), and it was more prevalent among younger patients and female sex (P < 0.0001). Five patients (0.4%) were determined to have gallbladder cancer, and the mean age of these cases was 65.6 ± 18.2 years. Two cases were Stage 2, two cases were Stage 3B, and one case was Stage 3A. There was no T1 or Tis tumor. Conclusion: Routine histopathological examination of gallbladder is significant with respect to the determination of additional interventions at the postoperative period required for cancer cases coincidentally diagnosed.
https://link.springer.com/article/10.1007/s12328-018-0927-4
https://www.sciencedirect.com/science/article/pii/S004681771830282X?dgcid=raven_sd_via_email
Gallbladder TNM staging, Margins, Survival
- Signet ring cancer of the gall bladder: a SEER database analysis
Minerva gastroenterologica e dietologica 2018 Nov;():
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30488679
- Patterns of Presentation, Treatment, and Survival Rates of Gallbladder Cancer: a Prospective Study at a Tertiary Care Centre
Journal of gastrointestinal cancer 2018 Sep;49(3):268-274
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=28367607
BACKGROUND: India has high incidence of gallbladder carcinoma with regional variation in incidence, the highest in Northern India. This study examines the patterns of presentation, treatment strategies, and survival rate of all patients with gallbladder cancer (GBC) evaluated at our tertiary academic hospital over a period of 2 years. METHODS: All patients presented to our institute with established tissue diagnosis of carcinoma gallbladder were accrued in our study over a time period of 2 years. Presentation, treatment modalities, and survival rates were analyzed. RESULTS: One hundred six patients were included: 80 females and 26 males (F: M = 3:1). Median age was 60 years. Eighty patients (75%) had gallstones and 20 patients (21%) had typical history of chronic cholecystitis. The common symptom and sign at presentation were pain in the right upper abdomen (81%) and lump abdomen (49%), respectively. Overall resectability rate was 19.8% (21/106). Eighty-five patients were unresectable or metastatic and treated with palliative intent. Stagewise distribution at diagnosis was stage I (0%), stage II (4%), stage IIIA (10%), stage IIIB (8%), stage IVA (17%), and stage IVB (61%). Estimated 1-year survival for stages II, IIIA, IIIB, IVA, and IVB was 100, 76, 47.4, 26, and 10.6%, respectively. Significant difference in OS was observed among different stages of GBC (p value <0.001). CONCLUSION: If proper investigations are done, radical surgery including multi-organ resection can be curative with acceptable morbidity and mortality. Stage at presentation and ability to perform curative resection are the most important prognostic factors predicting survival. Palliative chemotherapy should be considered for metastatic GBC.
- National Failure of Surgical Staging for T1b Gallbladder Cancer
Annals of surgical oncology 2018 Nov;():
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30499077
BACKGROUND: Current guidelines recommend radical cholecystectomy with regional lymphadenectomy (RC-RL) for patients with T1b gallbladder cancer (GBC). However, the extent to which these guidelines are followed is unclear. This study aimed to evaluate current surgical practices for T1b GBC and their implications for overall management strategies and associated outcomes. METHODS: This retrospective cohort study investigated patients identified from the National Cancer Data Base (2004-2012) with non-metastatic T1b GBC. The patients were categorized according to type of surgical treatment received: simple cholecystectomy (SC) or RC-RL. Among the patients who had lymph nodes pathologically examined, nodal status was classified as pN- or pN+. Use of any adjuvant therapy was ascertained. Overall survival (OS) was compared based on type of surgical treatment and nodal status. RESULTS: The cohort comprised 464 patients (247 SC and 217 RC-RL cases). The positive margin status did not differ between the two groups (6.1% for SC vs 2.3% for RC-RL; p = 0.128). For RC-RL, the pN+ rate was 15%. Adjuvant therapies were used more frequently in pN+ (53.1% vs 9.4% for pN-). By comparison, 10.9% of the SC patients received adjuvant therapy. The OS for RC-RL-pN- (5-years OS, 64.4%) was significantly better than for RC-RL-pN+ (5-years OS, 15.7%) or SC (5-years OS, 48.3%) (p < 0.001). CONCLUSION: Less than 50% of the patients with a T1b GBC primary tumor undergo the recommended surgical treatment. Given that 15% of these patients have nodal metastasis and in light of the previously described benefits of adjuvant therapy for node positive GBC, failure to perform RC-RL risks incomplete staging and thus undertreatment for patients with T1b GBC.
https://link.springer.com/article/10.1245/s10434-018-7064-7
Ampulla of Vater TNM staging, Margins, Survival
- Demographics, tumor characteristics, treatment, and clinical outcomes of patients with ampullary cancer: a surveillance, epidemiology, and end results (SEER) cohort study
Minerva gastroenterologica e dietologica 2018 Nov;():
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30488680
INTRODUCTION: Ampullary cancer accounts for only 0.2% of GI cancers. The objective of this study was to investigate the incidence, demographics, tumor characteristics, treatment, and survival of patients with ampullary tumors. METHODS: Data on ampullary cancer between 2004 and 2013 was extracted from the Surveillance, Epidemiology and End Results (SEER) Registry. The clinical epidemiology of these tumors was analyzed using SEER*Stat. RESULTS: A total of 6803 patients with ampullary cancer were identified. Median age at diagnosis was 71±13 years. The overall age-adjusted incidence of ampullary cancer was 0.59 per 100,000 per year. A higher incidence of ampullary cancer was observed in males compared to females (0.74 vs 0.48 per 100,000 per year). Most tumors were moderately differentiated (39.5%). The most common stage at presentation was Stage I (21%), followed by Stage II (20%). The majority (63%) of these tumors were surgically resected while 20% of patients received radiotherapy. One and 5-year cause-specific survival for ampullary cancer was 71.7% and 38.8% respectively, with a median survival of 31 months. On Cox regression analysis, Black race, increasing cancer stage and grade, N1 stage, and non-surgical treatment were associated with poorer prognosis. Those who were not treated with surgical intervention were at 4.5 times increased risk for death (Hazard Ration 4.5, 95% CI 3.93-5.09, P=0.000). CONCLUSIONS: The annual incidence of ampullary cancer has been fairly constant, though males are more likely to be affected. While its incidence increases with age, patients who are treated by surgical intervention have significantly better outcomes. Additionally, through the use of endoscopic techniques, ampullary cancer can be detected and treated much earlier.
PanNET, Pancreatic Neuroendocrine Tumors and related neuroendocrine neoplasms
- Clinicopathological characteristics of non-functioning cystic pancreatic neuroendocrine tumors
Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2018 Nov;():
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30497875
BACKGROUND/OBJECTIVES: The biological features of cystic pancreatic neuroendocrine tumors (PNETs) remain unclear. The aim of this study was to clarify the clinicopathological characteristics of non-functioning PNETs (NF-PNETs) with a cystic component. METHODS: The medical records of 75 patients with NF-PNETs who had undergone resection in our institution were retrospectively reviewed. Clinicopathological factors were compared between PNETs with and without a cystic component. Expression of somatostatin 2 receptor (SSTR-2) was also analyzed. RESULTS: Cystic PNETs were diagnosed in 14 patients (19%). The proportion of men was significantly higher for cystic than solid PNETs (79% vs. 44%, P < 0.05) and cystic PNETs were significantly larger than solid PNETs (25 mm vs. 17 mm, P < 0.01). However, there were no significant differences in the prevalence of lymph node metastases (14% vs. 10%, P = 0.64), hepatic metastasis (7% vs. 3%, P = 0.54), or disease-free survival rate (both 86%, P = 0.29) between PNETs with and without a cystic component. SSTR-2 expression was more frequently observed in PNETs with a cystic component than in those without (100% vs. 70%, P < 0.01). CONCLUSIONS: Although cystic PNETs were larger upon diagnosis than solid PNETs in this study, prognosis after surgical resection did not differ significantly between these types of PNET. Somatostatin receptor scintigraphy and somatostatin analogues may be more useful for diagnosing and treating cystic PNETs, respectively.
https://www.nature.com/articles/s41379-018-0110-y
https://www.sciencedirect.com/science/article/pii/S0046817718304350
- Prognosis of patients with neuroendocrine tumor: a SEER database analysis
Cancer management and research 2018 11;10():5629-5638
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30519109
Background: Neuroendocrine tumors (NETs) are a group of heterogeneous cancers arising from a variety of anatomic sites. Their incidence has increased in recent years. This study aimed to analyze the prognosis of NETs originating from different anatomic sites. Methods: We identified 73,782 patients diagnosed with NETs from the Surveillance Epidemiology and Ends Results (SEER) database from 1973 to 2014. Clinical data were compared between patients with different primary tumor sites using the chi-squared test. Differences in survival among NET patients with different tumor sites were compared by Kaplan-Meier analysis. Cox proportional hazard models were performed to identify the prognostic factors of overall survival. Results: In this cohort, the lung/bronchus was the most common site of NETs, accounting for 30.6%, followed by the small intestine (22.2%), rectum (16.2%), colon (13.4%), pancreas (10.8%), and stomach (6.8%). Totally, 73,782 patients were selected for this cohort from 1973 to 2014. The median survival duration was 41 months. The 1-, 3-, 5-, and 10-year overall survival rates for patients with NETs were 72.8%, 52.7%, 39.4%, and 18.1%, respectively. Patients with NETs located in the rectum had the best prognosis, followed by those with NETs in the small intestine (HR, 1.660, 95% CI, 1.579, 1.744), lung/bronchus (HR, 1.786, 95% CI, 1.703, 1.874), stomach (HR, 1.865, 95% CI, 1.755, 1.982), and colon (HR, 1.896, 95% CI, 1.799, 1.999). Patients with NETs in the pancreas had the highest risk of mortality (HR, 2.034, 95% CI, 1.925, 2.148). Conclusion: Significant differences in survival were found among various primary tumor sites. NETs in the rectum had the best prognosis, while those in the pancreas had the worst. Primary tumor sites might be one of the most useful outcome predictors in patients with NETs.
- ASO Author Reflections: Pancreatic Neuroendocrine Tumor Recurrence and Survival Predicted by Ki67
Annals of surgical oncology 2018 Dec;():
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30519760
https://www.sciencedirect.com/science/article/pii/S0046817718303009
Neuroendocrine Tumor Stroma Interactions, Microenvironment, Inflammatory Response
- Touch imprint cytology on endoscopic ultrasound fine-needle biopsy provides comparable sample quality and diagnostic yield to standard eus-fna specimens in the evaluation of solid pancreatic lesions
Cytopathology : official journal of the British Society for Clinical Cytology 2018 Nov;():
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30484917
OBJECTIVES: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the gold standard for the diagnosis of solid pancreatic lesions (SPLs). Cytological samples can also be obtained using touch imprint cytology (TIC) on EUS fine-needle biopsy (FNB) specimens. We aimed to compare sample quality and diagnostic yield of EUS-FNA-standard cytology (EUS-FNA-SC) to that of EUS-FNB-TIC in a series of patients with SPLs. METHODS: Thirty-two consecutive patients referred for EUS-tissue acquisition of SPLs who underwent rapid on-site evaluation (ROSE) of both EUS-FNA-SC and paired EUS-FNB-TIC during the same endoscopic session were retrospectively identified. Sample quality (evaluated in terms of blood contamination, presence of clots, tissue casts, cellularity, and necrosis) and diagnostic yield were compared between the techniques. RESULTS: The mean number of passes to reach diagnosis at ROSE was similar between EUS-FNA-SC and EUS-FNB-TIC (1.09 ± 0.3 vs 1.13 ± 0.34, P = .711). EUS-FNA-SC scores of sample quality were comparable to those of EUS-FNB-TIC (blood contamination, 2.47 ± 1.11 vs 2.25 ± 1.14, P = .109; clots, 1.25 ± 0.76 vs 1.19 ± 0.69, P = .624; tissue casts, 3.56 ± 0.88 vs 3.59 ± 1.09, P = .872; cellularity, 2.84 ± 1.11 vs 3.09 ± 1.09, P = .244; necrosis, 2.25 ± 1.08 vs 2.53 ± 1.02 P = .059; total score, 12.38 ± 2.88 vs 17.66 ± 2.38, P = .536). Adequacy, sensitivity and diagnostic accuracy of the two sampling techniques were equal (93.7%, 90.6%, 90.6%, respectively). CONCLUSIONS: EUS-FNB-TIC provides comparable samples to those of EUS-FNA-SC and combines the benefits of cytology and histology for the evaluation of SPLs by employing a single needle during the same endoscopic procedure. This article is protected by copyright. All rights reserved.
- Diagnostic Value of S100p, IMP3, Maspin, and pVHL in the Differantial Diagnosis of Pancreatic Ductal Adenocarcinoma and Normal/chronic Pancreatitis in Fine Needle Aspiration Biopsy
Journal of cytology 2018 12;35(4):247-251
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30498299
Introduction: Differentiation between pancreatic ductal adenocarcinoma (PDAC) from benign mimickers is a well-known problem in cytological materials. Recent studies incorporated biological markers into this question and some studies showed that expression of S100P, IMP3, and maspin as well as nonexpression of von Hippel-Lindau gene product (pVHL) were significantly correlated with PDAC. In this study, we aimed to investigate diagnostic value of maspin, IMP3, S100P, and pVHL immunostaining in fine needle aspiration biopsies (FNABs) of pancreatic lesions. Materials and Method: In all, 33 cases of FNAB cell blocks of PDAC and 34 cases of surgical non-neoplastic pancreas specimens which were retrieved from the archives slides from 2007 to 2011 were included in this study. All the cases were stained with maspin, IMP3, S100P, and pVHL. Expression patterns of markers were scored and compared with benign mimickers. Test performance of each antibody and possible antibody combinations were also evaluated. Results: The study was composed of 33 PDAC and 34 control cases (8 chronic pancreatitis, 3 mucinous cystic neoplasm, and 23 nontumoral pancreatic tissue of PDAC). Diagnostic sensitivity for malignancy in S100P, IMP3, and maspin was 84.8%, 81.8%, and 87.5%, respectively. Specificity of these three markers was 100%. Sensitivity and specificity of pVHL for detecting nontumoral pancreatic tissue were 100% and 81.8%, respectively. When maspin, IMP3, and S100P expression were used together as triple test, sensitivity was 62.5% and specificity 100%. However, when any two of each three markers were evaluated (triple test/dual response), sensitivity reached 93.8% and specificity 100%. Conclusion: We observed that dual response in triple test (positive staining with two of these three markers) of maspin, IMP3, and S100P immunocytochemistry is very sensitive and specific in differential diagnosis of PDA and non-neoplastic pancreatic lesions. pVHL may have an additional role, when triple assessment is not satisfactory.
https://onlinelibrary.wiley.com/doi/abs/10.1111/cyt.12662
- Advances in the cytologic diagnosis of gastroenteropancreatic neuroendocrine neoplasms
Cancer cytopathology 2018 Nov;():
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30485690
Two-thirds of neuroendocrine neoplasms arising in the human body originate from the gastrointestinal system or pancreas. Gastroenteropancreatic neuroendocrine neoplasms are heterogeneous, comprising both well differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The clinical presentation, molecular characteristics, and behavior are distinct for NETs and NECs. Fine-needle aspiration is an important modality for the primary diagnosis and staging of these neoplasms and can provide information of prognostic and therapeutic significance. Our evolving understanding of neuroendocrine neoplasm biology has led to several iterations of classification. In this review, new concepts and issues most relevant to cytology diagnosis of gastroenteropancreatic neuroendocrine neoplasms are discussed, such as newer detection methods that aid in diagnosis and staging, recent changes in World Health Organization classification, practical issues related to grading these neoplasms on cytology, guidelines for diagnostic reporting, and panels of immunohistochemical stains for the diagnosis of metastasis. The current understanding of genetic and epigenetic events related to tumor development and potential applications for cytology also are presented as they relate to prognostication and recent therapeutic advances.
https://onlinelibrary.wiley.com/doi/abs/10.1002/cncy.22073
- Mechanosignalling via integrins directs fate decisions of pancreatic progenitors
Nature 2018 12;564(7734):114-118
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30487608
The pancreas originates from two epithelial evaginations of the foregut, which consist of multipotent epithelial progenitors that organize into a complex tubular epithelial network. The trunk domain of each epithelial branch consists of bipotent pancreatic progenitors (bi-PPs) that give rise to both duct and endocrine lineages, whereas the tips give rise to acinar cells1. Here we identify the extrinsic and intrinsic signalling mechanisms that coordinate the fate-determining transcriptional events underlying these lineage decisions1,2. Single-cell analysis of pancreatic bipotent pancreatic progenitors derived from human embryonic stem cells reveal that cell confinement is a prerequisite for endocrine specification, whereas spreading drives the progenitors towards a ductal fate. Mechanistic studies identify the interaction of extracellular matrix (ECM) with integrin α5 as the extracellular cue that cell-autonomously, via the F-actin-YAP1-Notch mechanosignalling axis, controls the fate of bipotent pancreatic progenitors. Whereas ECM-integrin α5 signalling promotes differentiation towards the duct lineage, endocrinogenesis is stimulated when this signalling cascade is disrupted. This cascade can be disrupted pharmacologically or genetically to convert bipotent pancreatic progenitors derived from human embryonic stem cells to hormone-producing islet cells. Our findings identify the cell-extrinsic and intrinsic mechanotransduction pathway that acts as gatekeeper in the fate decisions of bipotent pancreatic progenitors in the developing pancreas.
https://www.sciencedirect.com/science/article/pii/S0039606018307402
December 2018Scientific Reports 8(1)
DOI: 10.1038/s41598-018-26526-x
- Identification of Key Potential Targets and Pathway for Arsenic Trioxide by Systemic Bioinformatics Analysis in Pancreatic Cancer
Pathology oncology research : POR 2018 Nov;():
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30506130
Arsenic trioxide is an approved chemotheraputic agent for the treatment of acute promyelocytic leukemia (APL). Recently, numerous studies suggested that arsenic trioxide acts as anti-cancer roles in various human malignancies. However, the molecular mechanisms are not fully elucidated. In this study, we explored the critical targets of arsenic trioxide and their interaction network systematically by searching the publicly available published database like DrugBank (DB) and STRING. Seven direct protein targets (DPTs) and 111 DPT-associated genes were identified. The enrichment analysis of arsenic trioxide associated genes/proteins revealed 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Among these pathways, phosphatidylinositol-4,5-bisphosphate-3-kinase -Akt (PI3K-Akt) single pathway and pancreatic cancer pathway are highly correlated with arsenic trioxide and have 5 overlapped targets. Then we investigated the gene alternation of selected critical genes in pancreatic cancer studies using cBio portal. These results indicated that arsenic trioxide could act anti-tumor function through PI3K-Akt single pathway and identified critical genes might be therapeutic targets for pancreatic cancer.
Molecular Techniques & Research Methods, Liquid Biopsy
Tumor Stroma Interactions, Microenvironment, Inflammatory Response, Microbiome
Molecular Pathology Preneoplastic and Preinvasive Lesions, PanIN, IPMN, MCN, ICPN
December 2018Scientific Reports 8(1)
DOI: 10.1038/s41598-018-25669-1
- MiR-1-5p is down-regulated in gallbladder carcinoma and suppresses cell proliferation, migration and invasion by targeting Notch2
Pathology, research and practice 2018 Oct;():
PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30497876
BACKGROUND: Numerous studies have demonstrated that aberrant microRNAs (miRNAs) are involved in tumorigenesis and tumor progression. Nevertheless, the precise role of miR-1-5p in gallbladder carcinoma cell growth and metastasis remains not fully revealed. MATERIAL AND METHODS: The levels of miR-1-5p were detected in gallbladder carcinoma tissues and cell lines using qRT-PCR method. A series of functional assays, including cell proliferation, colony formation, wound healing and Transwell invasion were conducted using miR-1-5p or miR-1-5p inhibitor transfected cells. RESULTS: MiR-1-5p was remarkably down-regulated in gallbladder carcinoma tissues and cell lines compared to normal. In addition, over-expression of miR-1-5p markedly suppressed the growth, migration and invasion of gallbladder carcinoma cell. Conversely, down-expression of miR-1-5p facilitated gallbladder carcinoma cell proliferation and aggressiveness. Mechanistic investigations demonstrated that neurogenic locus notch homolog protein 2 (Notch2) was the directly target of miR-1-5p and Notch2 mediated the inhibitory effect of miR-1-5p in gallbladder carcinoma cell growth and aggressiveness. CONCLUSION: Our findings demonstrated that miR-1-5p acted as a suppressive miRNA and played vital roles in the growth, migration and invasion of gallbladder carcinoma cell through targeting Notch2.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219964/
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